The experiments described here were designed to study interactions which occur between cerebro-vascular endothelial cells (EC) which comprise the blood-brain barrier (BBB) and peripheral blood lymphocytes. It was found that factors such as la antigen and the adhesion molecule, mala-2, play important roles in adhesion of lymphocytes to cultured EC. T lymphocytes capable of transferring experimental allergic encephalomyelitis (EAE) caused permeability changes in interferon (IFN)-treated (la-positive) EC. Antibodies to either la antigen or mala-2 partially inhibited these permeability changes. Treatment of EC with TNF resulted in increased adherence of T lymphocytes to EC and also augmented permeability changes of IFN-treated EC. Nonencephalitogenic T lymphocytes continued to adhere to EC, but did not induce permeability changes. These results indicate that EC-lymphocyte interactions may induce alterations in the permeability of the BBB leading to vascular egression into the CNS, which is a pathologic hallmark of neuromimune disorders such as EAE and multiple sclerosis. It was also found that EC co-cultured with immune lymph node cells resulted in the inhibition of lymphocyte proliferation to specific antigen. Experiments indicated that prostacyclin (PGI2) production by EC was responsible for the observed inhibition.